For 40 years, total cholesterol dominated cardiovascular risk assessment. The Framingham Heart Study established associations between elevated total cholesterol and heart disease risk, and the statin era was built on reducing this number. What subsequent research has established is that total cholesterol is a crude proxy for the more informative breakdown of its components, and that for many adults a normal total cholesterol number coexists with a lipid profile that is genuinely risky.
The Components That Matter
- LDL cholesterol: often called bad cholesterol; carries cholesterol from the liver to tissues; elevated levels are associated with increased atherogenicity, but particle size and number matter more than the total LDL mass measurement
- HDL cholesterol: often called good cholesterol; carries cholesterol from peripheral tissues back to the liver; below 1.0 mmol/L in men or 1.2 mmol/L in women is a major cardiovascular risk factor
- Triglycerides: the storage form of fat in the bloodstream; elevated fasting triglycerides, above 1.7 mmol/L, indicate insulin resistance and carbohydrate overconsumption; are an independent cardiovascular risk factor
- Non-HDL cholesterol: total cholesterol minus HDL; a better predictor of cardiovascular events than LDL alone because it includes all atherogenic lipoprotein fractions
- Triglyceride-to-HDL ratio: a ratio above 2.0 in mmol/L terms is a strong marker of insulin resistance and small dense LDL pattern; optimal is below 1.0
The Small Dense LDL Problem
LDL particles come in different sizes. Large fluffy LDL particles are relatively benign. Small dense LDL particles are more atherogenic because they are more readily oxidised, more easily enter the arterial wall, and are cleared by the liver less efficiently. Standard lipid panels measure LDL cholesterol, not LDL particle number or size. A person can have normal LDL cholesterol but elevated LDL particle number if many small, less cholesterol-rich particles are present. This pattern is reliably associated with high triglycerides, low HDL, and insulin resistance.
Sources
- Castelli, W.P. (1986). The triglyceride issue: a view from Framingham. American Heart Journal, 112(2), 432-437.
- Krauss, R.M. (2010). Lipoprotein subfractions and cardiovascular disease risk. Current Opinion in Lipidology, 21(4), 305-311.
- Emerging Risk Factors Collaboration. (2009). Major lipids, apolipoproteins, and risk of vascular disease. JAMA, 302(18), 1993-2000.